Submissions for variant NM_020435.4(GJC2):c.454GAG[6] (p.Glu158del)

dbSNP: rs746050475

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811598	SCV001159142	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001047776	SCV001211756	uncertain significance	Spastic paraplegia	2019-03-22	criteria provided, single submitter	clinical testing	This sequence change deletes 3 nucleotides from exon 2 of the GJC2 mRNA (c.472_474delGAG). This leads to the deletion of 1 amino acid residue in the GJC2 protein (p.Glu158del) but otherwise preserves the integrity of the reading frame. While this variant is present in population databases (rs746050475), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a GJC2-related disease. In summary, this is a rare single amino acid deletion with uncertain impact on protein function. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown.
PreventionGenetics, part of Exact Sciences	RCV003973020	SCV004798970	likely benign	GJC2-related disorder	2023-12-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).